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Marie-Agnès Bringer, Mayssa Albouery, Bénédicte Buteau, Marie-Annick Maire, Alain M Bron, Catherine Creuzot-Garcher, Niyazi Acar, Lionel Bretillon; The ApoB100,LDLR-/- mouse model as an experimental model to study aging of the retina: focus on autophagy, inflammation and oxidative stress.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1674.
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© ARVO (1962-2015); The Authors (2016-present)
Some tissue alterations such as accumulation of lipids at the basement of the retinal pigment epithelium and dysregulation of cellular processes that maintain homeostasis such as autophagy are thought to be key factors contributing to the development of age-related maculopathy. The ApoB100,LDLR-/- mouse model has been described to display cholesteryl ester deposition in the retina, together with an altered visual function. Here, we aimed at exploring whether this experimental model recapitulates others signs of aging retina such as an enhanced oxidative stress and inflammation, and an impaired autophagy.
Experiments were performed on retinas from young (4 to 8 weeks) ApoB100,LDLR-/- (n=8) and B6129SF2/J (control) mice (n=8), and elderly (84 to 113 weeks) control mice (n=4), from both sexes. The mRNA levels of autophagy-, inflammation- and oxidative stress-related genes were quantified by RT-qPCR. Autophagy, inflammation and oxidative stress were evaluated at the protein level by Western Blot and by immunostaining on cryosections. Statistical significance was calculated using a Mann-Whitney test.
Aging was associated in the retinas of control mice with a significant increase in the protein level of the autophagy-related protein 5 (ATG5) and accumulation of the autophagy marker LC3-II, and a significant decrease in the protein level of the autophagy receptor p62. The mRNA levels of the anti-oxidative stress response gene Hmox1, and the pro-inflammatory genes IFN-gamma, IL8/KC and TNFalpha tended to increase in the retinas of old mice compared to young control mice. Comparison of young ApoB100, LDLR-/- to control mice showed an increase in the accumulation of LC3-II in the retinas of ApoB100, LDLR-/- mice. In addition, the mRNA levels of Tfeb and Sirt1, which encode regulators of autophagy and longevity, tended to decrease and, the levels of Hmox1, IFN-gamma and IL8/KC mRNAs tended to increase in the retinas of young ApoB100, LDLR-/- mice compared to age-matched control mice.
Our data showed that inflammation and oxidative stress are enhanced in old mice and that autophagy is impaired with aging. Interestingly, we observed that these aging-related modifications were found in young ApoB100, LDLR-/- mice, supporting the relevance of this model to study aging of the retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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